Self-Assembled H-Bonding Superstructures for Alkali Cation and Proton Transport.

Transmembrane protein channels are of significant importance for the design of biomimetic artificial ion channels. Regarding the transport principles, they may be constructed from amphiphilic compounds undergoing self-assembly that synergistically generate directional superstructures across bilayer membranes. Particularly interesting, these alignments may impose an artificial pore structure that may control the ionic conduction and translocate water and ions sharing one pathway across the cell membrane. Herein, we report that the imidazole and 3-amino-triazole amphiphiles self-assemble via multiple H-bonding to form stable artificial networks within lipid bilayers. The alignment of supramolecular assemblies influences the conduction of ions, envisioned to diffuse along the hydrophilic pathways. Compounds 1-8 present subtle variations on the ion transport activities, depending the structure of hydrophilic head and hydrophobic components. Fluorinated compounds 3, 4 and 7, 8 outperform the corresponding non-fluorinated counterparts 1, 2 and 5, 6. Under the same conditions, the R enantiomers present a higher activity vs. the S enantiomers. The present systems associating supramolecular self-assembly with ion-transport behaviors may represent very promising unexplored alternatives for ion-transport along with their transient superstructures within bilayer membranes, paralleling to that of biology.

Structural Insights of Humins/Epoxidized Linseed Oil/ Hardener Terpolymerization.

Bio-based thermosetting resins were synthesized from a ternary composition: humins; epoxidized linseed oil (ELO); and an industrial hardener, Capcure3-800 (CAP). Humins are in a focused attention in the last years, as biorefinery by-product, therefore its valorization through materials design is very important. Here we present a structural study of terpolymerization of humins/ ELO/CAP. The reactivity of these systems was highlighted by in situ FT-IR and 1H and 13C NMR. The integration of humins in thermosetting resins gives alternatives to new feedstocks for future bio-based materials.

Oriented chiral water wires in artificial transmembrane channels.

Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.

Columnar Self-Assemblies of Triarylamines as Scaffolds for Artificial Biomimetic Channels for Ion and for Water Transport.

Triarylamine molecules appended with crown-ethers or carboxylic moieties form self-assembled supramolecular channels within lipid bilayers. Fluorescence assays and voltage clamp studies reveal that the self-assemblies incorporating the crown ethers work as single channels for the selective transport of K+ or Rb+. The X-ray crystallographic structures confirm the mutual columnar self-assembly of triarylamines and crown-ethers. The dimensional fit of K+ cations within the 18-crown-6 leads to a partial dehydration and to the formation of alternating K+ cation-water wires within the channel. This original type of organization may be regarded as a biomimetic alternative of columnar K+-water wires observed for the natural KcsA channel. Supramolecular columnar arrangement was also shown for the triarylamine-carboxylic acid conjugate. In this latter case, stopped-flow light scattering analysis reveals the transport of water across lipid bilayer membranes with a relative water permeability as high as 17 µm s-1.

Carbonic anhydrases activation with 3-amino-1H-1,2,4-triazole-1-carboxamides: Discovery of subnanomolar isoform II activators.

A series of ureas was prepared by reacting mono- or di- isocyanates with 3-amino-1H-1,2,4-triazole derivatives. The new carboxamides were investigated as activators of two human (h) carbonic anhydrases (CAs, EC 4.2.1.1), the physiologically relevant isoforms hCA I and II, considering the fact that they have structural resemblance to histamine, a well-known CA activator. Highly effective activators were detected in the series, with potency in the low nanomolar and subnanomolar range, depending on the substitution pattern at the 1,2,4-triazole ring and the nature of the linker between the two heterocyclic rings, in the case of the diureas. The most effective hCA II activator (KA of 0.05nM) ever reported has been evidenced in this study. Although CA activators do not have pharmacological applications for the moment, in animal models it has been shown that they enhance cognition, making them interesting for conditions in which CA activity is diminished, such as aging or Alzheimer's disease.

A class of carbonic anhydrase I - selective activators.

A series of ureido and bis-ureido derivatives were prepared by reacting histamine with alkyl/aryl-isocyanates or di-isocyanates. The obtained derivatives were assayed as activators of the enzyme carbonic anhydrase (CA, EC 4.2.1.1), due to the fact that histamine itself has this biological activity. Although inhibition of CAs has pharmacological applications in the field of antiglaucoma, anticonvulsant, anticancer, and anti-infective agents, activation of these enzymes is not yet properly exploited pharmacologically for cognitive enhancement or Alzheimer's disease treatment, conditions in which a diminished CA activity was reported. The ureido/bis-ureido histamine derivatives investigated here showed activating effects only against the cytosolic human (h) isoform hCA I, having no effect on the widespread, physiologically dominant isoform hCA II. This is the first report in which CA I-selective activators were identified. Such compounds may constitute interesting tools for better understanding the physiological/pharmacological effects connected to activation of this widespread CA isoform, whose physiological function is not fully understood.

Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation.

Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Špores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

Self-assembly of supramolecular triarylamine nanowires in mesoporous silica and biocompatible electrodes thereof.

Biocompatible silica-based mesoporous materials, which present high surface areas combined with uniform distribution of nanopores, can be organized in functional nanopatterns for a number of applications. However, silica is by essence an electrically insulating material which precludes applications for electro-chemical devices. The formation of hybrid electroactive silica nanostructures is thus expected to be of great interest for the design of biocompatible conducting materials such as bioelectrodes. Here we show that we can grow supramolecular stacks of triarylamine molecules in the confined space of oriented mesopores of a silica nanolayer covering a gold electrode. This addressable bottom-up construction is triggered from solution simply by light irradiation. The resulting self-assembled nanowires act as highly conducting electronic pathways crossing the silica layer. They allow very efficient charge transfer from the redox species in solution to the gold surface. We demonstrate the potential of these hybrid constitutional materials by implementing them as biocathodes and by measuring laccase activity that reduces dioxygen to produce water.

Multivalent recognition of concanavalin A by {Mo132 } glyconanocapsules--toward biomimetic hybrid multilayers.

Herein, we consider Müller's spherical, porous, anionic, molybdenum oxide based capsule, (NH4)42[{(Mo(VI))Mo(VI)5O21(H2O)6}12{Mo(V)2O4(CH3COO)}30]⋅10 CH3COONH4⋅300 H2O≡(NH4)42⋅1 a⋅crystal ingredients≡1, {Mo132}, as an effective sugar-decorated nanoplatform for multivalent lectin recognition. The ion-exchange of NH4(+) ions of 1 with cationic-sugars, D-mannose-ammonium chloride (2) or D-glucose-ammonium chloride (3) results in the formation of glyconanocapsules (NH4)(42-n)2n⋅1 a and (NH4)(42-m)3m⋅1 a. The Mannose (NH4)(42-n)2n⋅1 a capsules bind selectively Concanavalin A (Con A) in aqueous solution, giving an association avidity constant of K(a)(multi)=4.6×10(4) M(-1) and an enhancement factor of ß=K(a)(multi)/K(ass)(mono)=21.9, reminiscent of the formation of "glycoside clusters" on the external surface of glyconanocapsule. The glyconanocapsules (NH4)(42-n)2n⋅1 a and (NH4)(42-m)3m⋅1 a self-assemble in "hybrid multilayers" by successive layer-by-layer deposition of (NH4)(42-n)2n⋅1 a or (NH4)(42-m)3m⋅1 a and Con A. These architectures, reminiscent of versatile mimics of artificial tissues, can be easily prepared and quantified by using quartz crystal microgravimetry (QCM). The "biomimetic hybrid multilayers" described here are stable under a continual water flow and they may serve as artificial networks for a greater depth of understanding of various biological mechanisms, which can directly benefit the fields of chemical separations, sensors or storage-delivery devices.